EARLY STEPS IN DROSOPHILA SEX DETERMINATION

这项研究的目标是从分子角度理解早期 以果蝇性别决定途径的步骤为例 实验上易于处理的发育开关。 重点是 性致死调控基因，在短期开始时发挥作用 受性别特异性、替代性调节的基因等级 RNA剪接。 Sxl 生成的转录本被拼接成 在女性中为功能性形式，在男性中为非功能性形式。 尺寸 是在初始通路信号之后第一个被识别的基因， X 染色体与常染色体的比率。 Sxl 的早期回应是 以观察到的一组女性特异性转录本为特征 胚胎发生早期短暂；这些与 后来的转录本受剪接调节。 调控基因 控制这个早期步骤将被识别和表征 为了阐明能够区分的机制 一条和两条 X 染色体。 该方法将是设计遗传 筛选现有信号元件突变的抑制子，以及 筛选早期结合 Sxl 增强子的蛋白质 发起人。 调节蛋白之间以及与 DNA 之间的相互作用 将接受检查。 果蝇与人类发展的相关性已得到充分证实 根据同源框基因及其描述建立 哺乳动物胚胎中的表达模式。 的定义 果蝇性别决定等基因开关也可能是 有望为人类监管机制提供一个模型 发展。

The goal of this research is a molecular understanding of the early steps of the Drosophila sex determination pathway as an example of an experimentally tractable developmental switch. The focus is the regulatory gene Sex-lethal, which functions at the start of a short hierarchy of genes that are regulated by sex-specific, alternative RNA splicing. Sxl produces transcripts that are spliced into a functional form in females but a non-functional form in males. Sxl is the first identified gene after the initial pathway signal, the ratio of X chromosomes to autosomes. Sxl's early response is characterized by a set of female-specific transcripts observed transiently in early embryogenesis; these are distinct from the later transcripts regulated by splicing. Regulatory genes that control this early step will be identified and characterized in order to elucidate the mechanism capable of distinguishing between one and two X chromosomes. The approach will be to devise genetic screens for suppressors of existing signal element mutations, and to screen for proteins that bind enhancers of the Sxl early promoter. Interactions between regulatory proteins and with DNA will be examined. The relevance of Drosophila to human development has been well established with the description of homeobox genes and their pattern of expression in mammalian embryos. Definition of a genetic switch such as Drosophila sex determination may likewise be expected to provide a model for human regulatory mechanisms in development.